Cycloadditions with dichloroketene

Only a few ketenes can be isolated, and diphenylketene is one of those. The majority of the other ketenes dimerize quickly, as exemplified hy the parent ketene H2C=C=0. The fewer or smaller the substituents that are hound at the sp2-hybridized carbon atom the quicker these dimerizations proceed  

Cycloadditions with reactive ketenes therefore can he observed only when they are prepared in situ and in the presence of the alkene to which they shall he added. Dichloroketene generated in situ is the best reagent for intermolecular [2+2]-cycloadditions. Dichloroketene is poorer in electrons than the parent ketene and therefore more reactive toward the relatively electron-rich standard alkenes. The reason is that the dominating frontier orbital interaction between these reactants involves the LUMO of the ketene, not its HOMO (see Section 15.2.4). 

It is possible that a [4+2] -cycloaddition between the dichloroketene carbonyl group and the cyclopentadiene occurs. This would be followed by a Claisen rearrangement to give the product observed. The lesson is that you should learn what we think we know, but not be afraid to question it. That is science. 

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Enantioselective [2 + 2 cycloaddition.2 The chiral allylic ether (1), prepared from (lS,2R)-( + )-2-phenylcyclohexanol, undergoes enantioselective cycloaddition with dichloroketene to furnish, after one crystallization, optically pure (-)-2. This cyclobutanone after ring expansion and exposure to chromium(II) perchlorate gives... 

SCHEME 10.6 [2+2] Cycloadditions with dichloroketene directed by a galactose-derived auxiliary. 

With acrylonitrile, only [2-1-2] cycloadducts 6, 8 and 9 were obtained. Additionally, bromomethylenecyclopropane underwent a [2-1-2] cycloaddition with dichloroketene yielding 3-bromo-2,2-dichlorospiro[2.3]hexan-2-one. ... 

A four-carbon cyclo-enlargement of the cyclic thioketal (33) by a [4 + 2] cycloaddition with dichloroketen yields the 1,4-dithia-derivative (34). This is a potentially valuable route to many multifunctional dithia-macrocyclic systems. 

Camphorsulfonyl chlorides 45 readily form amides by reaction with amines. On reduction of the carbonyl group, alcohols, e.g., 46 and 47, are obtained which are extremely useful auxiliaries for many purposes. Thus, esters are formed with carboxylic acids which may then undergo enolate reactions (SectionsD.1.1.1.3.2., D.l.5.2.1., D.3. and D.7.1.) or act as dienophiles and dipolar-ophiles (Sections D.l.6.1.1.1.2.2.1. and D.l.6.1.2.1.). Enol ethers of these auxiliaries give [2 + 2] cycloadditions with dichloroketene (Section D.l.6.1.3.), while carbamate derivatives have been used in acyliminium reactions (Section D.l.4.5.). Generally, steric hindrance in the sulfonamide group improves the stereoselectivity of the reactions and, therefore, the amides with diisopropylamine and dicyclohexylamine are used as auxiliaries both enantiomers of the dicyclohexyl derivative are commercially available. 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

Dechlorination of 4,4-dichlorocyclobutenones.2 These products of [2 + 2] cycloaddition of dichloroketene with alkynes (9, 153) can be reduced satisfactorily and without isomerization by zinc dust in ethanol containing 5 equiv. each of acetic acid and a tertiary amine (preferably TMEDA). 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with N-bromosuccinimide from cyclo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - The present procedure, based on the last method, is relatively simple and uses inexpensive starting materials. Step A exemplifies the 2 + 2 cycloaddition of dichloroketene to an olefin, " and the specific oycloadduot obtained has proved to be a useful intermediate in other syntheses. " Step B has been the subject of several mechanistic studies, " and its yield has been greatly improved by the isolation technique described above. This synthesis has also been extended to the preparation of various tropolone derivatives. - " ... 

Cycloadditions give better efficiency and stereocontrol for ring formation. A high regioselectivity (95 5) for the cycloaddition of dichloroketene to a cyclohexene en route to synthetic eriolanin [164] has been observed. It appears that the allylic methoxy group play a dominant role. Note that the proximal sp2-carbon is a donor by virtue of its 1,3-relationship with the oxygen function. 

The application of chiral auxiliary groups which can be removed after the cycloaddition has met with limited success. The chiral auxiliary can be attached to either the ketene or alkene moiety. In a study of dichloroketene cycloadditions with a series of enol ethers 18, to which a chiral alkoxy group is attached, diastereoselectivities ranged from 55 to 90%,n with the choice of chiral auxiliary being crucial to obtaining the desired diastereoselectivity. 

In an extension of this method, the cycloaddition of dichloroketene to the heterocyclic aminomethyleneketone (341) yields the dihydropyranone which is dehydrochlorinated with DBN to the fused pyran-2-one (Scheme 104) (78JHC181). Similar behaviour is shown by the benzologue of the enamine. 

An ab initio study of the 2 + 2-cycloadditions of allene to isocyanic acid and ketene to vinylimine found the reactions to be concerted and mostly asynchronous.28,29 The diastereoselective 2 + 2-cycloaddition of dichloroketene with a chiral enol ether (26) produced the cyclobutanone (27), which leads to a key intermediate (28) in (g) the total synthesis of the natural alkaloid (-)-Swainsonine (29) (Scheme 8).30 The... 

Unlike ordinary alkenes, ketenes do 2 + 2 cycloadditions with themselves—the dimerisation above—and with other alkenes.1 Reaction of dichloroketene with cyclobutadiene 11 to give the... 

Fig. 12.31. Orientation-selective [2+2]-cycloaddition with in situ generated dichloroketene I the dichloroketene is generated by way of an NEt3-mediated fi-elimination of HC1 from dichloroacetyl chloride.

Au-Yeung and Fleming have devised a new alternative synthesis of loganin (590) based upon allylsilane chemistry.438 The bicyclic ketone 586, obtained by cycloaddition of dichloroketene to trimethylsilylcyclopentadiene, was monodechlorina-ted, ring expanded with diazoethane, and again dehalogenated prior to equilibration... 

Cyclobutenediones. A general route to these diones involves the regiospecific cycloaddition of dichloroketene to the phenylthio enol ether (1) of a ketone. The adduct (2) on treatment with triethylamine eliminates (J MsSCI and rearranges to 3. Peracid oxidation of 3 results directly in a cyclobutenedione (4). 

Enantiospecific addition to chiral vinyl sulfoxides. The cycloaddition of dichloroketene (11, 169-17(1) to optically pure (R)- or (S)-l-cyclohexenyl tolyl sulfoxides (1) leads to optically pure y-butyrolactoncs (2) with complete cnantiospecificity at the two chiral centers. A third hiral ew-center is introduced in the addition of monochloroketene. 

S.2 Cycloadditions Involving Ketenes We next present two examples of cycloadditions involving ketenes that invoke a bifurcating PES. The cycloaddition of ketene with cy clopentadiene had long been thought to simply give the formal [2-1-2] product, such as the reaction of cyclopentadiene 67 with dichloroketene 68... 

The most recent formal asymmetric synthesis of (+)-anatoxin-a was achieved through a highly diastereoselective [2+2] cycloaddition of dichloroketene with a chiral enol ether(63 Scheme 7.15) in order to reach the general stracture of 2,5-disubstituted pyrrolidine (66) for generating the acyliminum ion and getting the required bicycle skeleton (67) (Muniz et al. 2005). 

Cyeloaddition to silyl enol ethers. As expected, dichloroketene, generated from trichloroacetyl chloride and activated zinc, reacts with silyl enol ethers to form 3-silyloxy-2,2-dichlorocyclobutanones, usually in good yield. Cycloaddition does not obtain with dichloroketene generated from dichloroacetyl chloride and triethylamine. In some cases only acyclic products are formed, but these may arise by ring opening of intermediate cyclobutanones. ... 

I -CycloatUition, 22 222 2, 118 3, 87-88). Two reviews have been published recently on the 1,2-cycloaddition of dichloroketene to olefins and dienes. In general, the best yields of cyclobutanones are obtained when the dchydrochlorination of dichloroacetyl chloride with triethylamine is conducted between 30 and 50° in a hydrocarbon solvent containing an excess of the ketenophile. The following reactivity sequence has been observed in the behavior of various keienes with cyclopentene ... 

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